Apparatus and method for integrated sampling from closed and open sample containers

ABSTRACT

Integrated sampler apparatus and method are provided and include a sample liquid container support component which is operable to support both closed and open sample liquid containers thereon on a random basis. Sample liquids from the open sample liquid containers are presented directly to a sample liquid analysis system probe for access thereby; while sample liquids from the closed sample liquid containers, which take the form of sample liquid containers closed by sample needle-pierced stoppers, are transferred by virtue of a sampling needle assembly and connected sample liquid transfer conduits and transfer valve, to a sample liquid dispensing well for access by the same sample liquid analysis system probe. Air segmented rinse liquid is provided for the sampling needle, transfer conduits, transfer valve, and dispensing well to minimize sample liquid carryover with regard to the sample liquids from the closed containers; and a surfactant is included with the rinse to lubricate the sampling needle to facilitate the piercing thereby of the closed sample liquid container stoppers and minimize the generation of sample liquid-contaminating stopper particles to use with aqueous sample and rinse liquids, hydrophobic sample liquid transfer conduits, transfer valve, and dispensing well surfaces are provided; and an isolation liquid which selectively wets those surfaces to the substantial exclusion of the aqueous sample and rinse liquids, is utilized in conjunction with the rinse liquid to further minimize sample liquid carryover. The open sample liquid containers and the dispensing well are supported at essentially the same level relative to the probe to maximize sampling accuracy thereby. A detector is provided to detect sample liquid identification as supported from the sample liquid container support component, and to differentiate between open and closed sample liquid containers for operation of the sample liquid analysis system probe in accordance therewith.

This application is a division of application for U.S. patent, Ser. No.07/671,713 filed Apr. 4, 1991 by Mr. Kenneth F. Uffenheimer, now U.S.Pat. No. 5,201,232.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to new and improved apparatus and method forintegrated sampling from both closed and open sample liquid containersthrough use of the same sample liquid analysis system sampling probe.

2. Description of the Prior Art

Although combined open and closed tube sampling is known in the priorart as disclosed in my U.S. Pat. No. 4,756,201 issued Jul. 12, 1988, andassigned to the assignee hereof, there is no teaching or contemplationin that patent disclosure of configuring or operating the combinedsampler to make possible sampling from both closed and open sampleliquid containers through use of the same sample liquid analysis systemsampling probe; which, particularly in contemporary, high-speed andhighly accurate sample liquid analysis systems, is of somewhat fragileconfiguration and of precisely defined and strictly limited range ofhigh-speed travel and, as such, is totally inapplicable to sampling fromclosed sample containers by the piercing as required of the tubestoppers.

In addition, U.S. Pat. No. 4,756,201 representatively discloses theconsistent prior art requirements for separate and distinct sampleliquid container support components for the transport of closed and opensample liquid containers to and through the sampler, and for thesampling from those closed and open sample liquid containers atdifferent sampler locations; and further requires in accordance with theprinciples of the prior art that the respective closed and open sampleliquid containers be of essentially of the same configurations foreffective support and feed thereof as above; thereby renderingimpossible the totally random loading of both closed and open sampleliquid containers of markedly different configurations on the samesampler support component.

Too, and although sampler component rinse to minimize sample liquidcarryover, i.e. the contamination of a succeeding sample liquid by theresidue of a preceding sample liquid attendant successive sample liquidanalyses, and thereby maximize the accuracy of the successive sampleliquid analyses results, is known in the prior art, as also clearlydisclosed for example in my U.S. Pat. No. 4,756,201, as is the use ofhydrophobic sample liquid analysis system components and hydrophobicisolation liquids, or "oils" which selectively "wet" those components tothe substantial exclusion of aqueous sample liquids, again for thepurposes of sample liquid carryover minimization, as disclosed forexample in U.S. Pat. Nos. 3,479,141 and 4,253,846 to William J. Smythe,respectively issued Nov. 18, 1969 and Mar. 3, 1981, and assigned to theassignee hereof; no prior art sampler apparatus or method are knownwhich effectively combine these two procedures to result in overallsample liquid carryover minimization to levels well below those ofhighly stringent contemporary clinical significance, and to result inminimization of rinse liquid consumption and sampler time required forthe rinse cycle.

Also, no prior art sampler apparatus or method are known wherein aplurality of markedly different open sample liquid containers may besupported at essentially the same level from a common container supportcomponent, or wherein sample liquids from both open and closed sampleliquid containers may be readily presented at essentially the same levelto a sample liquid analysis system probe.

Further, although the use of a sampling needle for sampling from closedsample liquid tubes by the piercing of a tube stopper is, of course,well known in the prior art, again for example as clearly disclosed inmy U.S. Pat. No. 4,756,201, no prior art sampler is known wherein asurfactant and an isolation liquid as above are applied to the samplingneedle during needle rinse thereby effectively lubricating the same forthe piercing of the stopper(s) of subsequently supplied closed sampletube(s) to greatly facilitate such penetration and minimize stopperparticle generation, and attendant sample liquid contamination anddegradation in sample liquid analysis accuracy by such particles.

In summary, it may be understood that no prior sampler or related art isknown which discloses or makes obvious the hereindisclosed combinationsof sampler elements and sampling steps as respectively embodied in thesampler apparatus and sampling method of my invention.

OBJECTS OF THE INVENTION

It is, accordingly, an object of my invention to provide new andimproved apparatus and method for integrated sampling from closed andopen sample liquid containers.

It is another object of my invention to provide apparatus and method asabove which provide for sampling from both closed and open sample liquidcontainers through use of the same sample analysis system probe.

It is another object of my invention to provide sampler apparatus andmethod as above which enable the highly efficient, totally randomloading and transport of both closed and open sample liquid containersthrough use of the same sample liquid container carrier component.

It is another object of my invention to provide sampler apparatus andmethod as above which, through an effective combination of samplercomponent rinse and, for use with aqueous sample liquids, the use ofhydrophobic sampler component internal surfaces and a highly hydrophobicisolation liquid which selectively "wets" those surfaces to thesubstantial exclusion of aqueous sample liquids, are effective tominimize sample liquid carryover to levels previously unattainable bysampler apparatus and sampling methods.

It is another object of my invention to provide sampler apparatus andmethod as above which enable significant reduction in sampler rinseconsumption, and the "down" or non-sample-analysis time required for thesampler rinse cycle.

It is another object of my invention to provide sampler apparatus andmethod as above which, with regard to sampling from closed sample liquidcontainers through use of a sampling needle to pierce a closed samplecontainer stopper, provide for highly effective lubrication of thesampling needle to greatly facilitate the piercing of the containerstopper by the needle, thereby minimizing sample-contaminatinggeneration of particles of the container stopper, and maximizing theaccuracy of the sample analysis results.

It is another object of my invention to provide sampler apparatus andmethod as above which are readily operable to present sample liquidsfrom both closed and open sample liquid containers to the sampleanalysis probe at essentially the same sample liquid level, therebymaximizing the sampling accuracy of the sample analysis system probe.

It is another object of my invention to provide sampler apparatus andmethod as above which are readily operable to support a wide variety ofmarkedly different open sample liquid containers at essentially the samelevel from a common- support component to greatly facilitate theemplacement of a common evaporation cover thereover.

It is another object of my invention to provide sampler apparatus andmethod as above which are particularly adapted to highly satisfactoryoperation in conjunction with a wide variety of clinical sample analysisapparatus and methods.

It is a further object of my invention to provide sampler apparatus andmethod as above which require only the use of readily availablematerials and components of proven dependability in the fabricationthereof, and which are thus capable of long periods of satisfactory,essentially maintenance-free operation.

It is a still further object of my invention to provide samplerapparatus and method as above which are satisfactorily operable at highsampling rates fully commensurate with the high sample analysis rates ofcontemporary sample analysis systems.

SUMMARY OF THE INVENTION

As disclosed herein, the new and improved apparatus and method of myinvention for integrated sampling from closed and open sample liquidcontainers comprise a universal sample container carrier block includinga plurality of spaced, sample container mounting apertures formedtherein, and in each of which may be operatively mounted either a closedor open sample liquid container, thus enabling random sample liquidcontainer loading of the carrier block. The carrier block is indexableto place each of the sample liquid containers in turn at a samplingposition relative to a relatively fragile, high speed and preciselyoperable sample analysis system probe. Sample liquid container detectormeans are operatively associated with the carrier block and determinewhether the container is a closed or open sample container as the samereaches the sampling position. If it is an open sample liquid container,sampling is effected directly from the container by the probe. It if isa closed sample liquid container, sample transfer means which areoperatively associated with the carrier block operate to transfer sampleliquid from the closed sample container to sample liquid dispensingmeans which are accessible by the probe for sampling therefrom. Meansare provided to rinse the sample transfer and dispensing means with arinse liquid to remove sample liquid residue therefrom, therebyminimizing the contamination of a succeeding sample liquid by thatresidue. In addition, and for use with aqueous sample liquids, theinternal flow passages of the sample transfer and dispensing means arehydrophobic, and means are operatively associated therewith to introducean isolation liquid thereto which selectively wets those flow passagesto the substantial exclusion of the aqueous sample liquids therebyinhibiting the adherence of sample liquid residue thereto and furtherminimizing the contamination of succeeding sample liquids by theresidues of preceding sample liquids. The closed sample liquidcontainers take the form of sample tubes which are sealed by pierceablestoppers, and the sample transfer means include a sampling needle whichis operable to pierce those sample tube stoppers to withdraw sampleliquids therefrom. Means are provided to introduce a surfactant liquidwith the rinse liquid onto the sampling needle, and this operates tolubricate the same for the piercing of subsequent closed sample tubestoppers thereby minimizing the generation of tube stopper particles andthe contamination thereby of the sample liquids. The universal carrierblock sample container mounting apertures are configured to support allopen sample liquid containers at essentially the same level relative tothe carrier block; and this, in conjunction with the disposition of thesample liquid dispensing means also at essentially that same level,facilitates the presentation of all sample liquids from both closed andopen sample liquid containers to the analysis sytem probe at essentiallythe same sample liquid level, thereby insuring a full and consistentsample "pull" for the probe of all sample liquids from each of the openand closed sample containers, with resultant maximization of the sampleliquid analysis results. In addition, this facilitates the placement ofan evaporation cover over a "loaded" carrier block, or group thereof, toprevent sample liquid evaporation from the open sample containers priorto sampling and analysis.

DESCRIPTION OF THE DRAWINGS

The above and other objects and significant advantages of my inventionare believed made clear by the following detailed description thereoftaken in conjunction with the accompanying drawings wherein;

FIG. 1 is an exploded perspective view of integrated closed and opensample container sampling apparatus representatively configured andoperable in accordance with the teachings of my invention;

FIG. 2 is a top plan view of the universal sample container carrierblock of the sampling apparatus of FIG. 1;

FIG. 3 is a partial cross-sectional view taken generally along line 3--3in FIG. 2;

FIG. 4 is a bottom plan view of the universal sample container carrierblock of the sampling apparatus of FIG. 1;

FIG. 5 is a cross-sectional view taken generally along line 5--5 in FIG.1;

FIG. 6 is a cross-sectional view taken generally along line 6--6 in FIG.3;

FIG. 7 is a top plan view of the universal carrier block drive shuttleof the sampling apparatus of FIG. 1;

FIG. 8 is a cross-sectional view taken generally along line 8--8 in FIG.7;

FIG. 9 is a bottom plan view of the drive shuttle of FIG. 7;

FIG. 10 is a top plan view of the sampling needle and needle driveassembly of the sampling apparatus of FIG. 1;

FIG. 11 is a side plan view of the assembly of FIG. 10;

FIG. 12 is an enlarged, fragementary cross-sectional view of thesampling needle, needle sleeve, drive shuttle, carrier block and closedsample container of FIG. 1;

FIG. 13 is an enlarged cross-sectional view of the sampling needle andsleeve assembly of FIG. 12;

FIG. 14 is a flow diagram for the sampling apparatus of FIG. 1;

FIG. 15 is a schematic diagram illustrating the electrical control andsynchronization circuit for the sampling apparatus of FIG. 1; and

FIG. 16 is a timing diagram illustrating the respective operations ofthe control components of the sampling apparatus of FIG. 1 as drawn tothe same time scale.

DETAILED DESCRRPTION OF THE INVENTION

Referring now to the patent application drawings, an automated,integrated sampler representatively configured and operable inaccordance with a best mode of the teachings of my invention forrandomly sampling from both closed and open sample liquid containersthrough use of the same sample analysis system probe is indicatedgenerally at 20 in FIG. 1.

Sampler 20 comprises operatively associated universal sample containercarrier block as indicated generally at 22; carrier block drive shuttleas indicated generally at 24; fixed drive shuttle support member asindicated generally at 25; closed sample container and sample liquididentification detector as indicated generally at 26; closed samplecontainer sample needle and needle drive assembly as indicated generallyat 28; a multiport sampling valve as indicated generally at 30; samplepump as indicated generally at 32; closed sample container pressureequalization chamber as indicated generally at 34; an open sampleaspiration well as indicated generally at 36; and a sample analysissystem sampling probe as indicated generally at 37; respectively.

Flexible conduits of standard, generally inert plastic laboratorytubing, for example Teflon, are indicated at 38, 40, 42 and 44 in FIG.1, and respectively connect the closed sample container sampling needle46 of assembly 28, pump 32, equilibration chamber 34, and sampleaspiration well 36 as shown to different ports of sampling valve 30;while a like conduit as indicated at 48 forms a volumetric loop betweenstill different ports of the sampling valve 30. Conduits of the sameconfiguration as above are indicated at 50 and 52 and respectivelyextend from sampling valve 30, and equilibration chamber 34, to vacuumand therefrom to waste, as indicated on drawing FIG. 1.

A sample liquid edge detector is indicated at 54 and is operativelydisposed as shown in conduit 42 between sampling valve 30 andequilibration chamber 34, and a sample particle trap is indicated at 56and is operatively disposed as shown in conduit 44 between samplingvalve 30 and sample aspiration well 36; both for purposes described indetail hereinbelow.

Flexible rinse liquid and isolation liquid supply conduits are indicatedat 58 and 60, and respectively extend from pumped sources of the same,as illustrated and described in detail hereinbelow with regard todrawing FIG. 13, into communication with sample aspiration well 36;while flexible rinse and isolation liquid supply conduits are alsoindicated at 62 and 64 and extend as shown from those same pumpedsources into communication with the sample needle 37 in mannerillustrated and described in detail hereinbelow with regard to FIGS. 12and 13.

Referring now to FIGS. 1 through 6 of the application drawings for moredetailed description of the universal carrier block 22, the same willreadily be seen to comprise a generally slab-like body member 70 inwhich are formed as shown a plurality of equally spaced, generallyidentical and vertically extending universal sample container mountingapertures as indicated at 72, 74, 76, 78, 80 and 82, respectively, inFIGS. 1, 2, 3 and 4; with each of the sample container mountingapertures extending as shown through the top wall 83 of the carrierblock body member 70 so as to be readily accessible from above thecarrier block 22. In addition, the respective opposed side walls 85 and87 of the carrier block body member 70 are cut-away as indicated at 84and 86 to provide for light transmission between certain of theaperture-mounted sample containers and the detector 26 for purposesdescribed in detail hereinbelow.

As best seen in FIGS. 3 and 4, each of the universal carrier blocksample container mounting apertures extends substantially through thecarrier block body member 70 from the top to the bottom thereof toterminate at the bottom wall 88 of the block; and this bottom wall iscentrally pierced for each of the mounting apertures by identical,closed sample container sampling openings as shown at 90, 92, 94, 96, 98and 100 in FIGS. 3 and 4. Aligned, arcuate mounting grooves 102 and 104are formed as best seen in FIGS. 3 and 1 in the upper portions of theopposed wall surfaces 106 and 108 of each of the sample containermounting apertures 72, 74, 76, 78, 80 and 82; and the aligned upperextremeties of the mounting apertures are also arcuately grooved in eachinstance as indicated at 110 and 112 in FIGS. 3 and 1; both for purposesdescribed in detail hereinbelow. As best seen in FIG. 1, aligned,generally vertically extending mounting slots 114 and 116 are formed inthe side wall 85 of the carrier block body member 70 to either side ofthe cut-away portion 84 of that body member side wall for each of theapertures 72, 74, 76, 78, 80 and 82, again for purposes described indetail hereinbelow.

A respresentative array of different sample containers, and operativelyassociated sample container liquid identification, and sample containermounting, components, is indicated generally at 118 in FIG. 1 to clearlyillustrate the particularly advantageous, universal sample containercarrying capability of the carrier block 22. More specifically,representative sample container array 118 includes a standard opensample liquid cup 120 of, for example, 1 milliliter capacity, withsuitably attached adapter and sample liquid identification card, asindicated at 119 and 122, respectively; a standard open sample liquidcup as above, and cup mounting adapter, as respectively indicated at 124and 126; a standard sample liquid tube, for example a Vacutainer, closedand sealed by a readily pierceable stopper, as respectively indicated at128 and 129, and a closed sample liquid tube retainer member asindicated at 130; and a standard open sample liquid tube as above asindicated at 132, and within which is operably disposed an automaticliquid level adjusting and filtering device as indicated at 134, and asdisclosed in U.S. Pat. No. 4,602,995 issued Jul. 29, 1986 to Michael M.Cassaday, et al, and assigned to the assignee hereof. Device 134functions to automatically adjust the level of the sample liquid in tube132 to a predetermined, precisely repeatable level relative to tube 132for optimal access by a sample liquid analysis system probe as describedin detail in U.S. Pat. No. 4,602,995; and the disclosure of U.S. Pat.No. 4,602,995 is hereby incorporated by reference herein.

Open sample liquid cup 120, and adapter 119 and identification card 122are operatively mounted in aperture 82 and slots 114 and 116 of thecarrier block 22 by the simple insertion of the card 122 into the slots114 and 116 for that aperture, and of the adapter 119 and 120 intoaperture 82, and the downward movement of the card and cup until thecard comes to rest with the cup securely supported as best seen in FIG.3 in the carrier block 22, with the cup lip 121 at a predetermined levelabove the upper surface 83 of the carrier block 22. With the cup 120 andidentification card 122 mounted as described in carrier block aperture82, it will be clear that identification card will be readily"accessible" by detector 26 of FIG. 1 for positive identification of thesample liquid container in cup 120.

Open sample cup 124 is operatively mounted in carrier block mountingaperture 80 as indicated and seen in FIGS. 1 and 3 by disposing the cupin adapter 126 and inserting the resultant cup-adapter combination inthe aperture from above, with the upper lip 127 of adapter 126 fittingprecisely as shown in FIG. 3 into the mounting grooves 110 and 112 ofthe mounting aperture 80; it being noted that adapter 126, which is madefor example from a resilient plastic, is of greater diameter thancarrier block mounting aperture 80 and is vertically split as shown at136 in FIG. 1. Thus, disposition as seen in FIG. 3 of the samplecup-adapter combination in mounting aperture 80 results in aparticularly secure fit of the same therein due to the requiredcompression of the resilient, split adapter 136. FIG. 3 makes clear thatsample cup 124 is supported as described in carrier block mountingaperture 80 so that the cup lip 125 is at essentially the same levelrelative to the upper carrier block surface 83 as lip 121 of cup 120;and this, assuming cups 124 and 120 to be filled to substantially thesame sample liquid level relative to the cup lips, is of particularlysignificant advantage with regard to insuring consistent access to thesample liquids contained in cups 120 and 124 by the sample liquidanalysis system probe 37 as discussed in greater detail hereinbelow.Although not shown, it will be clear to those skilled in this art thatmounting as described of the open sample cup-adapter combination 124,126 in carrier block mounting aperture 80 in accompanied by the simpleinsertion of an appropriate, flat sample liquid identification card inthe relevant mounting slots 114 and 116 for aperture 80 to positivelyidentify the sample liquid contained in cup 124 to detector 26.

Stoppered, closed sample tube 128 is operatively disposed in carrierblock mounting aperture 78 by the simple insertion of the tube thereintofrom above with the stopper side down as indicated and seen in FIGS. 1and 3, respectively. Thereafter, closed sample tube retainer 130--which,as best seen in FIG. 3, comprises a generally tubular body member 138including enlarged body member cap 140 and radial projections 142 and144, and a generally tubular retainer member 146 including lower end cap148 slidably disposed therewithin and spring-biased downwardly by coilspring 150--is inserted into the mounting aperture 78 above the closedsample container, with concave lower surface 149 of end cap 148 in firmabutment with the bottom of tube 128, and retainer body memberprojections 142 and 144 extending as shown into the cut-away portions 84and 86 of the carrier block body member side walls 85 and 87. Theretainer 130 is then pushed firmly downward against the action of spring150 until projections 142 and 144 are in vertical alignment with arcuatemounting apertuate grooves 102 and 104 of aperture 78; whereupon theretainer 130 is twisted to place those projections in those grooves andthen released to firmly secure the closed sample tube 132 in themounting aperture 78 as shown in FIG. 3. FIG. 1 makes clear that theclosed sample tube 128 includes a sample liquid identification label 152affixed to the outside thereof and identifying the sample liquidcontained therein; and that the tube 128 is disposed in mountingaperture 78 of the carrier block 22 in such manner that the label 152 isin alignment with the cut-away portion 84 of the carrier block side wall85 to insure light transmission between that identification label andsample liquid identification detector 26 thus providing for immediate"reading" of the label by the detector. Alternatively, a flat sampleliquid identification card as heretofore described may be inserted incarrier block card mounting slots 114 and 116 for mounting aperture 78to identify the sample liquid in closed tube 128; or both may be used,with only the card being "read" by detector 26. In addition, enlargedclosed sample container retainer cap 140 is, for example, renderedhighly light-reflective as by the affixation of a highly reflectivestrip 141 thereto as seen in FIG. 1, or color-coded, or both, so as tobe immediately discernible by the detector 26 as indicative of a closedsample container in carrier block mounting aperture 78.

Open sample tube 132, with liquid level adjusting and filtering device134 operatively disposed therein, is operatively disposed in carrierblock mounting aperture 76 by the simple insertion of the same thereintofrom above until the shoulder 154 of the device 134 comes to preciserest as best seen in FIG. 3 in the arcuate mounting aperture grooves 110and 112 to securely support both the device 134 and the tube 132 inmounting aperture 76. An identification label as indicated at 156 inFIG. 1 is affixed to open sample tube 132 and disposed as shown inalignment with the cut-away portion 84 of carrier block mountingaperture 76 for "reading" by detector 26 to positively identify thesample liquid in open sample tube 132. Again, as made clear by FIG. 3,the upper lip 158 of the sample liquid level adjusting and filteringdevice 132 is supported from the carrier block 22 as described atessentially the same level above the upper carrier block surface 83 asare the respective upper lips 121 and 125 of open sample cups 120 and124.

Further included in representative sample liquid container and supportcomponent array 118 are an open micro-sample cup and cup-mountingadapter, as respectively depicted in phantom at 160 and 162 in FIG. 1.Micro-sample cup 160 is depicted as taking the form of that disclosed inU.S. Pat. No. 4,758,409 issued Jul. 19, 1988 to Kenneth F. Uffenheimer,and assigned to the assignee hereof; and, as such, automaticallyfunctions to insure that the level of a small quantity of sample liquid,for example 100 microliters, container therein is maintained preciselyat the upper lip 164 of an inner sample liquid vessel 166 which isincluded therein as described in detail in U.S. Pat. No. 4,758,409, thedisclosure of which is hereby incorporated herein. Adapter 162 is of thesame configuration and manner of utilization as that previouslydescribed for adapter 126; and it will thus be clear to those skilled inthis art that operative mounting of the micro-sample cup-adaptercombination 161-162 in carrier block mounting aperture 74 would beessentially the same as that heretofore described for the mounting ofopen sample cup 124 and adapter 126 in carrier block mounting aperture80. An identification card, not shown, is inserted as previouslydescribed in card mounting slots 114 and 116 for carrier block mountingaperture 74 to positively identify the sample liquid contained inmicro-sample cup 160 to detector 26.

Although not shown, it will be understood that mounting as described ofthe micro-sample cup 160 and adapter 162 in carrier block mountingaperture 74 results in the disposition of the upper lip 168 of themicro-sample cup 160 at precisely the same level above the upper surface83 of the carrier block body member 70 as that depicted in FIG. 3 foropen sample cups 120 and 124, and for liquid level adjusting device 134in open sample tube 132.

Of particular advantage with regard to universal carrier block 22 is thefact that the essentially identical configurations of the respectivesample container mounting apertures 72, 74, 76, 78, 80 and 82, and thefull compatability of each of those mounting apertures to the operablemounting therein of either closed or open sample containers, enable theready and convenient operable mounting of closed or open samplecontainers in each of those mounting apertures as described on a trulyrandom basis; and further, without regard in each instance to theparticular configuration of the sample container in question. This, ofcourse, greatly facilitates the loading of the closed and open samplecontainers in the universal carrier block 22; and totally eliminates thepossibility of error in such sample container loading by rendering itliterally impossible to put the "wrong" container in any particularcarrier block sample container mounting aperture.

Referring now to FIGS. 1, 7, 8, 9 and 12 for more detailed descriptionof the universal carrier block drive shuttle 24, the same will readilybe seen to comprise an elongate body member 170 which is generallycoextensive in length with the carrier block 22, and which includes agenerally central groove 172 extending generally longitudinally thereof.Spaced, generally vertically extending drive lugs are indicated at 174,176, 178 and 180; and extend upwardly as seen in FIGS. 1 and 8 from theupper surface 182 of the drive shuttle body member 170 intocomplementally configured drive slots 182, 184, 186 and 188 formed asbest seen in FIG. 4 to extend through the bottom surface 88 of theuniversal carrier block 22, to thereby mechanically connect the driveshuttle 24 to the carrier block 22 upon the disposition of the block onthe suttle with the bottom surface 88 of the carrier block 22 resting onand supported from the top surface 182 of the drive shuttle 22 as bestshown in FIG. 12.

Further included in the drive shuttle 24 are spaced, closed samplecontainer sampling apertures as respectively indicated at 190, 192, 194,196, 198 and 200 which, upon operative disposition as described of thecarrier block on the drive shuttle, will respectively align with theclosed sample container sampling apertures 90, 92, 94, 96, 98 and 100(FIG. 4) at the under surface of the carrier block 22; thereby providingimmediate sampling access for the sampling needle 46 to the stopper(s)129 of closed sample tube(s) 128 as may be disposed in any of thecarrier block mounting apertures 72, 74, 76, 78, 80 and/or 82.

A generally longitudinally extending gear rack 202 is formed as bestseen in FIGS. 8, 9 and 12 at the underside of the drive shuttle 24 so asto be coextensive with the drive shuttle body member 170. The rack 202is interrupted in part as made clear in FIG. 9 by the spaced samplingapertures 190, 192, 194, 196, 198 and 200. The drive shuttle 24 furthercomprises spaced, longitudinally extending lower support edges 204 and206 which extend below the rack 202 as made clear for support edge 206by FIG. 8.

As beat seen in FIG. 1, the fixed drive shuttle support member 25comprises spaced support plates or the like 208 and 210 which extendlongitudinally of the drive shuttle 24; and FIGS. 1 and 12 make clearthat the drive shuttle is disposed thereon and supported therefrom bydisposition of the respective drive shuttle support edges 204 and 206 onthe spaced support plates 208 and 210 with freedom for slidable movementrelative thereto in the direction(s) of the longitudinal drive shuttleaxis.

A pinion gear is indicated at 212 in FIG. 12 and extends as shownupwardly through the space 214 (FIG. 1) between support plates 208 and210 to drivingly mesh with the drive shuttle gear rack 202; whereby willbe clear that driven rotation of the pinion 212 by operatively connecteddrive motor means, for example an electric drive motor as indicatedschematically at 213 in FIG. 12, in the clockwise direction as indicatedin FIG. 12 will be effective to slidably move the drive shuttle 24, andthe operatively connected universal carrier block 22, relative to thesupport plates 208 and 210 to the right as indicated by the arrow inFIG. 12; it being noted in this regard that the width of the gear rack202 as seen in FIG. 9 is sufficiently larger than the like diameters ofthe sampling apertures 190, 192, 194, 196, 198 and 200 to insure thatthe latter are not large enough to break the driving connection betweenthe pinion 212 and the rack 202, despite the partial interruption of therack by those apertures.

Closed sample container and sample liquid identification detector 26,which is fixedly disposed as shown in FIG. 1 adjacent the side wall 85of the universal carrier block 22, may take the form of any two of awide variety of readily available electro-optical devices respectivelycommensurate with the "reading" thereby of the various sample containeridentification cards and labels to positively identify the respectivesample liquids contained therein; and with the detection of the enlargedcap 140 of the closed sample container retainer member 130 to alert theintegrated sampler 20 of my invention to the fact that a closed samplecontainer is operatively disposed as described in a carrier blockmounting aperture of interest. More specifically, for sample liquididentification card and label reading, detector 26 may comprise a laserscanner of the nature marketed as Model #MS-500 by Microscan Systems,Inc., 939 Industry Drive, Tuckwalla, Wash. 98188; while, for detectionof the highly reflective surface of strip 141 on enlarged retainermember cap 140, detector 26 may comprise a photo-electric sensing deviceof the nature marketed as Model #PS-46 by Keyence Corp. of America,20610 Manhattan Place, Torrance, Calif. 90501. FIG. 1 makes clear thatdetector 26 is disposed immediately adjacent the universal carrier block26 essentially in line with sample analysis system prove 37 for reasonsset forth in detail hereinbelow.

Referring now to FIGS. 1, 10, 11, 12 and 13 for more detaileddescription of the closed sample container sampling needle and needledrive assembly 28, the same will readily be seen to comprise avertically extending, generally L-shaped fixed support bracket 216disposed below fixed drive shuttle support plates 208 and 210, andcomprising spaced support plates 218 and 220 affixed thereto andextending perpendicularly thereof. Spaced support shafts 222 and 224extend vertically between support plates 218 and 220; and a needlesleeve support bracket 226 is slidably mounted on those support shaftswith freedom for vertical movement relative thereto. A tubular samplingneedle sleeve 228, comprising a central sampling needle bore 230 (FIG.12), and a connected rinse and isolation liquid supply bore 232extending perpendicularly to bore 230, is fixedly attached to the uppersurface of support bracket 226 and extends vertically upward therefromas shown. A sleeve drive motor is shown at 234 in FIG. 11, and issupported from support shaft 222. Sleeve drive motor 234 may take anysuitable form, for example a valve controlled, double-acting pneumaticdrive motor, and is operable to drive sleeve support bracket 226, andsleeve 228, between the retracted sleeve position as shown in solidlines in FIG. 12, and the extended sleeve position as shown in phantomin FIG. 12.

A support shaft is indicated at 236 in FIG. 11, and extends verticallydownward of and is fixedly supported from sleeve support bracket 226. Asampling needle support bracket is indicated at 238 and is slidablysupport from shaft 236 with freedom for vertical movement relativethereto. Bracket 238 is spring-biased as best seen in FIG. 11 away frombracket 226 by a coil spring 239. Tubular sampling needle 46 issupported as shown from bracket 238 to extend vertically upwardtherefrom through sampling needle bore 230 in tubular sleeve 228. Asampling needle drive motor, again for example taking the form of avalve-controlled, double-acting pneumatic drive motor, is indicated at242 in FIG. 11, and is supported from shaft 236. Drive motor 242 isoperable independently of sleeve drive motor 234 to drive samplingneedle support plate 238, and sampling needle 46, between the retractedsampling needle position as shown in solid lines in FIGS. 12 and 13, andthe extended sampling needle position as shown in phantom in FIG. 12.Conduit 38 is operatively connected to the sampling passage, not shown,in tubular sampling needle 46 as indicated in FIG. 12.

Closed sample container sampling valve 30 preferably takes the form of aconventional, two-way, multi-port shear valve having a fixed upper (atleast as seen in FIG. 1) valve body member 250, and a mating, lowervalve body member 252 rotatable relative thereto as indicated by thearrow in FIG. 1 by a suitable drive motor, again for example avalve-controlled, double-acting pneumatic motor as indicatedschematically at 254 in FIG. 1. A shear valve of this nature isdisclosed in U.S. Pat. No. 4,756,201 issued Jul. 12, 1988 to Kenneth F.Uffenheimer, and assigned to the assignee hereof; and the disclosure ofU.S. Pat. No. 4,756,201 is hereby incorporated by reference herein.

Valve body member 252 is rotatable by drive motor 254 relative to valvebody member 250 between the position thereof depicted in FIG. 1 whereinthe valve connects conduits 38 and 42 through volumetric loop conduit48, and conduit 44 to conduit 50; and a non-illustrated valve bodymember position wherein the valve connects conduit 40 to conduit 44through the volumetric loop conduit 48; all for purposes described indetail hereinbelow.

Equilibration chamber 34 is of the same configuration and manner ofoperation as disclosed for the like component in U.S. Pat. No.4,756,201.

Sample pump 32 is a highly accurate, positive displacement pump taking,for example, the form of a standard syringe pump, and comprising a pumpcylinder 256, and a pump plunger 258 extending therefrom. A suitabledrive motor, again for example a valve-controlled, double-actingpneumatic drive motor, is shown schematically at 260 in FIG. 1, and isoperatively connected as indicated to syringe pump plunger 258 tooperate the pump.

Sample liquid dispensing well 36 comprises a vertically oriented,generally cylindrical body member 262 taking the general form of acontainer having a frusto-conical bore 264 formed therein and connectedas shown at the bore bottom to conduit 44. As annular inlet groove asindicated at 266 is formed as shown in body member 262 at the upperportion of bore 264; and flow passages, not shown, are formed in thebody member 262 connecting the respective rinse and isolation liquidsupply conduits 62 and 64 to inlet groove 266 for the supply of thoseliquids to groove 266, and the downward flow therefrom under the forceof gravity over the entire surface of bore 264 to conduit 44. Althoughnot made clear by FIG. 1, it may be understood that dispensing well 36is fixedly disposed relative to carrier block 22 so that the upper lip267 of the dispensing well is at essentially the same level as therespective upper lips of the open sample container disposed thereon asdescribed hereinabove. Dispensing well 36 is supported at that level byany appropriate support means as indicated schematically at 265 inFIG. 1. A container of this general nature is disclosed in detail in thecopending, continuation application for U.S. patent, Ser. No. 9,424,filed Feb. 2, 1987 to Michael M. Cassaday, et al, and assigned to theassignee hereof; and the disclosure of that copending application ishereby incorporated by reference herein.

Sample analysis system probe 37 may take any form appropriate to thesuccessive insertions of the same into, and the withdrawals in turn oflike quantities of sample liquids from, the respective open samplecontainers mounted as mounted in detail hereinabove in universal carrierblock 32 as the block is indexed past the probe, or from the sampledispensing well 36, all as described in detail hereinbelow; and thesuccessive supply of the thusly withdrawn sample liquids in turn inconventional manner to an operatively associated, automated sampleliquid analysis system as indicated schematically at 270 in FIG. 1, andto which probe 37 is operatively connected by an appropriate flexibleconduit as indicated schematically by line 271. To this effect, probe 37is moveable under the control of a probe drive motor as indicatedschematically at 272 in FIG. 1, between the respective depictedpositions of the probe wherein the same is disposed precisely above thecenter of a relevant open sample container on the universal carrierblock 22, and precisely above the center of the dispensing well 36,respectively; and is further reciprocable from those positions into andout of the sample liquids contained in those open sample containers orthe dispensing well, as the case may be, to precisely equal extents andfor precisely equal periods of time, thereby insuring that preciselyequal qauntities of sample liquid are withdrawn therefrom by the probe37 for supply in turn to the sample liquid analysis system 270.

Under these circumstances, it will be clear to those skilled in this artthat probe 37 is, of necessity, of somewhat fragile configuration and,in any event, totally inapplicable to direct sample from a closed samplecontainer such as tube 128 by the piercing as required of the tubestopper 129. In addition, it will be clear that, for use incontemporary, particularly high speed and highly accurate automatedsample liquid analysis systems, probe 37 is strictly limited in residentaspiration time in each of the sample liquid containers, and striclylimited in terms of the accelerations which can be impressed upon theprobe, and the velocities at which the probe can be moved, whenever theprobe is to any extent immersed in a sample liquid, or contains thesame, in order to insure that at least precisely the same amount ofsample liquid is aspirated by the probe and supplied in each instance tothe sample liquid analysis system 270; all in the interests of themaximization of the accuracy of the successive sample liquid analysisresults as described in some detail in my U.S. Pat. No. 4,758,409. Thus,it becomes of significant advantage to sample liquid analysis accuracythat all open sample containers of any nature as operatively mounted inuniversal carrier block 22, and the dispensing well 36, be disposed atessentailly the same level relative to probe 37; thereby greatlyfacilitating the "filling" thereof to essentially the same sample liquidlevel in each instance, and maximizing the accuracy of the sample liquidanalysis results. As discussed hereinabove, this is automaticallyaccomplished by micro-sample cup 160, and by liquid level adjustingdevice 134 in open sample liquid tube 132, which automatically fill tothe same level; and, with regard to dispensing well 262, isautomatically accomplished by virtue of the retention in volumetric loopconduit 48 of precisely the same sample liquid volume from each of theclosed sample liquid tubes 128 for supply in turn as described to thedispensing well. For open sample liquid cups 120 and 124, this isaccomplished by the "filling" thereof with sample liquids to essentiallythe same level in each instance relative to the upper cup lips 121 and125. A representative, automated sample liquid analysis system probe foruse as disclosed in conjunction with the integrated sampler 20 of myinvention, and one which advantageously incorporates the use of anappropriate isolation liquid for purposes of minimization of sampleliquid carryover as described, is disclosed in U.S. Pat. No. 4,121,466issued Oct. 24, 1978 to Allen Reickler, et al, and assigned to theassignee hereo; and the disclosure of U.S. Pat. No. 4,121,466 is herebyincorporated by reference herein.

An additional advantage of significant provided for by the dispositionas described of all open sample liquid containers at essentially thesame level relative to the upper surface 83 of the universal carrierblock 22 resides in the fact that this greatly facilitates the placementof a common evaporation cover, not shown, over a "loaded" carrier block,or group thereof, to prevent sample liquid evaporation from the opencontainers while the same are awaiting presentation in turn to thesample liquid analysis system probe 37 for sampling; and this would beof particular advantage with regard to evaporation prevention from thesmall quantities of sample liquids as contained in the micro-sample cups160.

Sample liquid edge detector 54 may take the form of an electricalconductivity detector as disclosed in U.S. Pat. No. 4,756,201 which isoperable to detect the passage of the leading edge of a sample liquidthrough conduit 42 on the basis of the resultant change in electricalconductivity across the conduit, and to generate and output anelectrical conductivity across the conduit, and to generate and outputan electrical signal indicative. Alternatively, and in instances whereinconduit 42 is light-transmittive, detector 54 may be of electro-opticalconfiguration.

Sampler particle trap 56 takes the form of a filter of pore size or meshsize appropriate to the trapping of all particultate matter above apredetermined size as may be contained in the sample liquids flowedtherethrough in the direction of dispensing well 36.

Suitable valves, for example standard normally open solenoid controlledpinch valves are depicted schematically at 274, 276, 278, 280 and 282 inFIG. 1; and are respectively operatively associated as shown withconduits 58, 50, 42 (to both sides of equilibration chamber 34), and 60,to control liquid flow therethrough as described in detail hereinbelow.

With regard to materials, universal carrier block 22 and drive shuttle24 are preferably injection molded from high strength plastics; closedsample container sampling needle preferably machined from particularlyhigh-strength steel, needle drive assembly 28 in general machined fromany appropriate metal with the exception of sleeve 228 which ispreferably an injection molded plastic. Shear valve body members 250 and252 are preferably formed and machined from appropriate, high strengthceramics. Dispensing well 36 is a machined plastic; while syringe pump32 comprises a glass cylinder and plastic tipped, metal plunger.Equilibration chamber 34 is formed from drawn glass tubing. All systemconduits are preferably of conventional, generally inert transparentlaboratory plastics.

For use of the integrated sampler 20 of my invention with aqueous sampleliquids, and a suitable isolation liquid to minimize sample liquidcarryover and maximize the accuracy of the sample liquid analysisresults as described in greater detail hereinbelow, it will beunderstood that the sleeve 228, conduit 38, the operative surfaces ofthe non-illustrated internal passages in sampling valve 30 which connectconduit 38 to volumetric loop conduit 48 and the latter to conduit 44,conduit 44, and dispensing well 36 are made or surface coated as thecase may be from selected ones of a range of readily available, inertand highly hydrophobic ones of a range of readily available, inert andhighly hydrophobic solid materials such as fluorinated or perflourinatedhydrocarbons of low surface energy and proven chemical stability, forexample, Teflon; while the isolation liquid is preferably constituted byany one of a range of fluorinated or perflourinated, highly hydrophobicliquids which are also inert and chemically stable, and which alsoexhibit low surface tension and appropriate viscosity; it being clearthat such isolation liquid will preferentially "wet" to a marked degreethose solid fluorinated or perfluorinated hydrocarbon materials to thevery substantial exclusion of the aqueous sample liquids. Nonlimitativeexamples of these solid and liquid hydrocarbons arepolytetrafluoroethylene and perfluorodecalin, respectively.

With the relevant components of my integrated sampler 20, and theisolation liquid, constituted as described materials-wise, it will beclear that the provision of an extremely thin layer of the isolationliquid in manner described in detail hereinbelow on the internalsurfaces of those sampler components, concomitantly with the flow of thesample liquids over those surfaces will result in that isolation liquidlayer preferentially "wetting" or adhering to those surfaces to thesubstantial exclusion of the sample liquids; thereby very greatlyinhibiting, if not totally preventing, sample liquid carryover, namelythe contamination of a succeeding sample liquid by the residue of apreceding sample liquid, with attendant, and contemporarilyunacceptable, degradation in the accuracy of the sample liquid analysisresults. This is of particular significance in, for example,contemporary clinical analyzers wherein highly accurate sample liquidanalysis results down to sample liquid constituent levels of 1 part per100,000 or less are absolutely required.

Referring now to the schematic flow diagram of FIG. 14, the same clearlyillustrates the control of pinch valves 274, 276, 278, 280 and 282 bysolenoids as schematically indicated at 284, 286, 288, and 292,respectively.

Four way valves are schematically depicted at 294, 296, 298 and 300 inFIG. 14; and are respectively operably connected as indicated in thepressurized fluid supply conduits of double acting pneumatic drivemotors 234, 242, 254 and 260; and to a standard, non-illustrated sourceof pressurized fluid, for example air, to control the respectiveoperations of those drive motors. Drive motor valve control solenoidsare schematically depicted at 302, 304, 306 and 308 in FIG. 14; and arerespectively operatively connected as indicated to valves 294, 296, 298and 300 to control the operations thereof, and thus of the drive motors234, 242, 254 and 260; thereby controlling at any point in time therespective positions of the sampling needle sleeve 228, the samplingneedle 46, the lower body member 252 of sampling valve 30, and plunger258 of syringe pump 32 in pump cylinder 256.

An open source of a suitable rinse liquid, which contains a surfactantto lubricate sampling needle 46 and thereby facilitate penetrationthereby of closed sample container stopper 129 as described in detailhereinbelow, is indicated at 310 in FIG. 14; and a supply conduit 312,including check valve 314, extends thereinto as shown. A vacuum-operateddiaphragm pump is depicted schematically at 316, and is operated asshown by a three-way, normally closed control valve 318 to which areconnected a source of vacuum V as indicated on line 320, and a source ofpressurized fluid P on line 322. Pumping conduit 324 extends as shownfrom pump 316 and includes a check valve 325; and conduit 312 joins withconduit 324 as indicated at 326 upstream of the valve. A valve controlsolenoid is indicated schematically at 328 in FIG. 14, and isoperatively connected as indicated to valve 318 to control the operationthereof, and thus of pump 316. As shown, pumping conduit 324 isconnected through valves 274 and 282 to rinse liquid supply conduits 58and 62 for supply of rinse liquid therethrough to passage 230 insampling needle sleeve 228, and bore 264 of dispensing well 36,respectively.

A source of a suitable isolation liquid as above, or "oil" as the samehas now come to be commonly termed in this art, is indicatedschematically at 330 in FIG. 14, and an isolation liquid supply conduit332 extends thereinto as shown. Conduit 332 connects as indicated witheach of conduits 60 and 64; and respective pump rollers of aconventional peristaltic pump an indicated schematically at 334 and 336are operatively associated as shown with conduits 60 and 64 to pumpliquids therethrough. A peristaltic pump electric drive motor as shownschematically at 338, and operates as indicated to drive pump rollers334 and 336 to thereby provide precisely predetermined and extremelysmall quantities of the isolation liquid from source 330 to sleevepassage 230 and dispensing well bore 264 upon drive motor actuation.

Referring now to the schematic circuit diagram of FIG. 15, a systemcontroller taking, for example, the form of an appropriately programmedmicro-processor or like device, is depicted schematically at 350; and isoperatively electrically connected as indicated to all electricallypowered components of the integrated sampler 20 of my invention, and tothe sample liquid analysis system 270 to which sample liquids are to besupplied in turn by that sampler, to control and synchronize as requiredthe respective operations thereof. More specifically, system controller350 is electrically connected as indicated by lines 352 and 354 todetectors 26 and 54, respectively, and is electrically connected asindicated by lines 356, 358, 360 and 362 to solenoids 302, 304, 306 and308 to input control signals thereto to control and synchronize therespective operations of the sleeve drive motor 234, the needle drivemotor 242, the sampling valve drive motor 254, and the sample pump drivemotor 260; thereby controlling and synchronizing the respectiveoperations of the sleeve 228, the sampling needle 46, the sampling valve30 and the sample pump 32.

Lines 364 and 366 electrically connect system controller 350 to shuttledrive motor 213 and probe drive motor 272 to control and synchronize therespective operations of the drive shuttle and 24 and the sampling probe37; while lines 368 and 370 electrically connect the controller 350 toisolation liquid pump drive motor 338, and the control solenoid 328 forrinse liquid pump drive motor control valve 318 to thereby control andsynchronize the respective operations of the isolation liquidperistaltic pump rollers 334 and 336, and the rinse liquid pump 316.Controller 350 is also electrically connected as indicated by lines 370,372, 374, 376 and 378 to control and synchronize the respectiveoperations of the pinch valve control solenoids 284, 286, 288, 290 and292; thereby controlling and synchronizing the supply of rinse liquid tothe sleeve passage 230, the drain of sample and rinse liquids by vacuumto waste through conduit 50, the connection of the equilibration chamber34 to the sampling needle 46 for pressure equilibration of the closedsample container 128 as described in detail hereinbelow, the connectionof the equilibration chamber 34 to vacuum and waste for the drain ofexcess sample liquid therethrough, and the supply of the rinse liquid todispensing well 36, respectively. System controller 350 is alsoelectrically connected as indicated by line 380 to the sample liquidanalysis system 270 to synchronize and control the operation of theintegrated sampler 20 of my invention in accordance with the operationof that sample liquid analysis system, and vice versa.

The timing diagram of FIG. 16 illustrates the operational conditions ofthe indicated components of the integrated sampler 20 of my invention asdrawn to the same time scale. More specifically, in FIG. 16 waveforms384, 386, 388, 390 and 392 respectively illustrate the operationalconditions of sampler valves 294, 296, 274, 298 and 300; while waveforms394, 396, 398, 400 and 402 respectively illustrate the operationalconditions of sampler valves 278, 280, 276, 282 and 318. Waveform 404illustrates the operational condition of isolation liquid pump drivemotor 338.

In operation of the integrated sampler 20 of my invention for samplingby probe 37 from an open sample container, for example micro-sample cup160 in universal carrier block mounting aperture 74, it will be clearthat as the carrier block 22 is indexed under control of systemcontroller 350 by driven movement as described of drive shuttle 24 bydrive motor 213 to place cup 160 in "sampling" position relative toprobe 37, the probe is actuated by drive motor 272 via system controller350 to move downwardly from the retracted position thereof asillustrated in FIG. 1 to the non-illustrated extended position thereofto immerse the inlet end 382 of the probe in the sample liquid containedin cup 160 for a precisely predetermined period of time to aspirate aprecisely predetermined sample liquid quantity therefrom for supply tosample liquid analysis system via conduit 271; whereupon the probe isremoved from that sample liquid and cup 160, and returned to theillustrated retracted position thereof. Concomitantly, theidentification data for the sample liquid contained in the micro-samplecup 160 as appears on the non-illustrated sample liquid identificationcard operatively disposed heretofore described in mounting slots 114 and116 for carrier block mounting aperture 74 is "read" by sample liquididentification detector 26 and outputted to system controller 350 online 352 for supply in turn by the controller to the sample liquidanalysis system 270 on line 380 to insure exact correlation between thatsample liquid and the analysis results therefor.

Since micro-sample cup 160 is an open sample container and, as such,does not include an enlarged cap 140 with reflective strip 141, nosignal indicative of a closed sample container in universal carrierblock mounting aperture 74 will be outputted by detector 26 to systemcontroller 350; whereby closed sample container sampling needle andneedle drive assembly 28, sampling valve 30, and sample pump 32 will notbe activated attendant sampling as described from micro-sample cup 160.

Immediately following sampling as described from micro-sample cup 160,carrier block 22 is again indexed as described to place open sample tube132 in "sampling" position relative to prove 37, whereupon sampling ofthe sample liquid from liquid level adjusting device 134 in that tube byappropriate movement of probe 37 as described is accomplished; againwith concomitant detection and outputting by detector 26 of the sampleliquid identification data from label 156 on tube 132. Again, since tube132 is an open sample container and does not include cap 140, no signalis outputted from detector 26 to controller 350 for activation of theclosed tube sampling needle drive assembly 28 and related integratedsampler components as specified hereinabove with regard to sampling fromopen micro-sample cup 160.

Significantly, since both micro-sample cup 160 and liquid leveladjusting device 134 function as described to retain the respectivesample liquids contained therein at the same level relative to the uppersurface of the universal carrier block 22, and thus at the same levelrelative to the inlet end 382 of the probe 37, the travel of which isprecisely fixed as described, it will be clear that immersion of theprobe to the same extent in the respective sample liquid samplecontained in cup 160 and tube 132 is insured; thereby in turn insuringconsistent and complete sample liquid aspiration by probe 37 from eachof cup 160 and tube 132 for supply to sample liquid analysis system 270with attendant maximization of the accuracy of the sample liquidanalysis results as set forth hereinabove.

Immediately following sampling as described from tube 132, universalcarrier block 22 is again indexed as described through appropriateactuation of shuttle drive motor 213 by system controller 350 on line364 to place closed sample tube 152 in sampling position which, in thisinstance, is most relevantly defined in accordance with FIG. 12 whereinaligned sampling apertures 96 of the carrier block 22 and 196 of thedrive shuttle 24 are disposed directly above sampling needle 46 andsleeve 228 and in direct alignment therewith. As carrier block 22 comesto rest in this position, the highly reflective surface of strip 141 onclosed tube retainer end cap 140 is detected by detector 26, and anelectrical signal indicative thereof outputted by the detector to systemcontroller 350 on line 352 to key the integrated sampler 20 of myinvention to the fact that sampling from a closed rather than opensample container must now be accomplished. As this occurs, systemcontroller 350 activates probe drive motor 272 on line 366 to move probe37 from the retracted position thereof of FIG. 1 directly over thecarrier block 22 to the retracted position thereof of FIG. 1 directlyover the sample liquid dispensing well 36.

Concomitantly, and making reference now to waveform 384 of FIG. 16, itwill be seen that controller 350 activates solenoid 302 on line 356 toshift valve 294 and operate sleeve drive motor 234 to rapidly movesleeve 228 vertically upward into and through drive shuttle aperture 196from the retracted to extended sleeve positions of the sleeve asrespectively depicted in solid and phantom lines in FIG. 12. After avery brief time delay to insure that drive shuttle and carrier blocksampling aperture alignment is correct and has permitted upward movementof the sleeve 228 as described, thus insuring that the way is clear forupward movement of the sampling needle 46, controller 350 activatessolenoid 304 on line 358 to shift valve 296 as indicated by waveform 386in FIG. 15 to operate sampling needle drive motor 242 to rapidly movethe sampling needle 46 vertically upward into and through the aligneddrive shuttle and carrier block sampling apertures 196 and 96 from theretracted to extended sampling needle positions as respectively depictedin solid and phantom lines in FIG. 12; with resultant piercing of theclosed sample tube stopper 129 by the sampling needle, and thedisposition of the sampling needle inlet end 408 in the sample liquid410 contained in the sample tube 128. Since, as made clear by waveform394 of FIG. 16, sample aspiration valve 278 is open as sampling needle46 pierces closed tube stopper 129, equilibration of the pressure withinclosed sample tube 128 with the atmospheric pressure then prevailing inequilibration chamber 34, through the open needle end 408, conduit 38,sampling valve 30, volumetric conduit loop 48, sampling valve 30, andconduit 42 will then immediately occur, all in the manner and to thesignificant advantages with regard to insuring a full and consistentsample "pull" by needle 46 from closed sample tube 128 as disclosed indetail in my U.S. Pat. No. 4,756,201.

Waveform 396 of FIG. 15 makes clear that pressure equilibration inclosed sample tube is virtually immediately followed by the activationon line 376 by controller 350 of solenoid 290 to open sample aspirationcontrol valve 280, thereby connecting equilibration chamber 34 and theopen sampling needle end 408 to vacuum through conduit 52; whereuponaspiration of the sample liquid 410 from closed tube 128 is commencedthrough needle 46, conduit 38, sampling valve 30, volumetric loopconduit 48, sampling valve 30, conduit 42, the equilibration chamber 34,and conduit 52 which connects the same to vacuum as indicated on FIG. 1.However, as the leading edge of the thusly aspirated sample liquid 410from closed sample tube 128 reaches sample liquid edge detector 54 inconduit 42, thus insuring that volumetric loop conduit 48, which is ofcourse upstream of detector 54, is completely filled with a preciselypredetermined quantity of the sample liquid 410, edge detector 54outputs a signal indicative thereof to system controller 350; whereuponthe controller activates solenoid on line 344 to close sample aspirationvalve 278, as made clear by waveform 394 of FIG. 16, therebydiscontinuing the aspiration of sample liquid 410 for closed sample tube128.

Discontinuation as described of sample liquid aspiration from closedsample tube 128 is virtually immediately followed as illustrated bywaveforms 384 and 386 of FIG. 15, by operation of system controller 350to activate solenoids 302 and 304 on lines 356 and 358 to shift valves294 and 296 to operate the sleeve and sampling needle drive motors toreturn the sleeve 28 and sampling needle 46 to the respective retractedpositions thereof of FIG. 12; and by the activation by controller 350 ofsolenoid 328 on line 370 to shift valve 318 to operate rinse liquid pump316 to commence the pumping of rinse liquid as illustrated by waveform402 in FIG. 16. Concomitantly, system controller 350 activates solenoid306 on line 360 to shift valve 298 as shown by waveform 390 in FIG. 16to operate sampling valve drive motor 254 to rotate valve body member252 relative to valve body member 250 to the non-illustrated relativepositions thereof wherein the volumetric loop conduit 48 connectsconduit 40 to conduit 44; thereby connecting sample pump 32 todispensing well 36 through the sampling valve 30. As this is completed,system controller 350 activates solenoid 308 on line 362 to shift valve300 as shown by waveform 390 in FIG. 15 to operate pump drive motor 260to actuate sample pump 32 to pump a major portion, for example 250 ml ofan available 300 ml, of the sample liquid 410 contained in volumetricloop conduit 48 therefrom through conduit 44 into bore 264 of thedispensing well 36, with particle trap 56 functioning to prevent thepassage of any particulate matter as may be contained in the sampleliquid into the dispensing well 36. As this is completed, systemcontroller again activates solenoid 306 on line 360 to shift valve 306as shown by waveform 390 in FIG. 16 to operate drive motor 254 to returnthe sampling valve 30 to the FIG. 1 position thereof; and, throughsolenoid 308, valve 300 and drive motor 260 deactivates and resetssample pump 32 as shown by waveform 392 in FIG. 16.

Immediately upon the deactivation of sample pump 32, controller 350activates probe drive motor 272 on line 366 to move probe 37 from theretracted to extended positions thereof into the sample liquid 410 nowsupplied as described to the dispensing well 36 for sampling thereof andsupply of a precisely predetemined sample liquid quantity to sampleliquid analysis system 270 via conduit 271, and immediate return of theprobe 37 to the retracted probe position. This makes clear that theintegrated sampler 20 of my invention functions in full accordance witha stated object thereof to provide for sampling from closed samplecontainers through use of a relatively fragile sample analysis systemprobe which had heretofore been restricted to sampling from open samplecontainers, only. In addition, it will be clear that disposition asdescribed of the sample dispensing well 36 at the same level relative toprobe 37 as that of the open sample containers on universal carrierblock 22 again maximizes the accuracy of the sample liquid analysisresults as discussed in detail hereinabove.

Concomitantly with the return as described of the sampling valve 30 tothe depicted sample liquid aspiration position thereof, controller 350activates solenoid 284 on line 370 to open valve 274 as shown bywaveform 388 to commence the flow of the rinse and surfactant liquids tothe tubular passage 230 in sleeve 28 through conduit 58, and thus to theopen tip 408 of the sampling needle 46; thereby thoroughly rinsing theexterior of the sampling needle of the residue of sample liquid 410, andlubricating with the surfactant liquid the sampling needle tip 48 andrelevant exterior surface thereof to greatly facilitate the penetrationthereby of the stopper of a succeeding closed sample container tominimize stopper particle generation and attendant contamination therebyof the sample liquid from that succeeding closed sample liquidcontainer. System controller 350 then also activates peristaltic pumpdrive motor 338 on line 368 as shown by waveform 404 in FIG. 16 tooperate pump rollers 334 and 336 to commence the flow of the isolationliquid from source 330 in conduits 332, 60 and 64 to the tubular sleevepassage 230 and the bore 264 of the dispensing well 36, respectively. Inaddition, system controller 350 then activates solenoid 288 on line 374to reopen aspiration valve 278 as shown by waveform 394 in FIG. 16; andthis, in conduction with aspiration valve 280 which remains open asshown by waveform 392, results in the aspiration of the rinse andsurfactant liquids from sleeve passage 230 through the open tip 408 ofthe sampling needle 46, the sampling needle, conduit 38, the internalpassage in sampling valve 30 which now again connects conduit 38 toconduit 48, conduit 48, the internal passage in sampling valve 30 whichnow again connects conduit 48 to conduit 42, conduit 42, theequilibration chamber 34, and conduit 52, respectively, to vacuum andwaste as indicated in FIG. 1. In addition, an extremely small quantityof the isolation liquid is flowed with the rinse and surfactant liquidsfrom sleeve passage 230 through the entire sample liquid aspiration pathas described; and this small isolation liquid quantity functions toreplenish the thin isolation liquid layer which coats the same inaccordance with the aspiration as described of sample liquids frompreceding closed sample containers.

The particularly advantageous inclusion of significant quantities of airwith the rinse and surfactant liquids which flow as described fromsleeve passage 230 through the open sampling needle tip 408 to vacuumand waste as described is provided for by predetermining the level ofthe non-illustrated vacuum source to provide a total fluid flow rate QTwhich is significantly greater than the fluid flow rate QRST at whichthe rinse, isolation and surfactant liquids are supplied to sleevepassage 330 by rinse liquid pump 316. Thus, supply of the rinse andsurfactant liquids as described to sleeve passage 230 will result in thesame flowing upwardly and swirling around in that passage essentially toor slightly above the level of the open sampling needle tip 408 asclearly illustrated by the liquid flow arrows in FIG. 13, thereby verythoroughly cleansing from the relevant upper exterior portions 407 ofthe sampling needle 46 any residue of the sample liquid 410 from tube128, the mixture at that level with the ambient air which is rapidlyflowing into the open end 420 (FIGS. 12 and 13) of the tubular sleevepassage 230 below drive shuttle 24, and the rapid flow of the resultantrinse liquid-air mixture into the sampling needle 46 through open needletip 408 for flow therefrom through the sampling needle and the entiresample liquid aspiration path to waste through conduit 52.

This admixture as described of the ambient air with the rinse liquidgreatly enhances the scrubbing action thereof on the open needle tip 408and interior passage 409 of the sampling needle 46, and greatly enhancesthe scrubbing action thereof on the hydrophobic isolation liquid-coatedinternal surfaces of conduit 38, the internal passages of sampling valve30 which connects conduit 38 to volumetric loop conduit 48, volumetricloop conduit 48, and the internal passages of sampling valve 30 whichconnect volumetric loop conduit 48 to conduit 42; whereby will beimmediately clear to those skilled in this art that virtually allresidue of the sample liquid 410 from closed sample tube 128 will beremoved therefrom by this rinse liquid-air mixture. Thus sample liquidcarryover from the closed sample container sample liquid aspiration pathupon the aspiration as described of a sample liquid from a succeedingclosed sample container is virtually eliminated, or certainly reduced tolevels well below those of highly stringent contemporary clinicalsignificance, for example, one part of a preceding sample liquid in100,000 parts of a succeeding sample liquid. In addition, the use ofambient air as described along with the rinse and surfactant liquidsgreatly reduces the consumption by the integrated sampler 20 of myinvention of the rinse and surfactant liquid solution with regard tosample liquid carryover minimization attendant sampling from closedsample containers, and this operates to render the sampler apparatus andmethod of my invention essentially independent of a high capacity orconstantly flowing source of those liquids; it being noted in thisregard that prior art samplers are known which require as much as 25liters per hour of rinse 1. Also, this reduction as described in theamount of rinse liquid required significantly reduces the amount ofrinse liquid which is of necessity left behind in the sample liquid flowpath, and this in turn significantly reduces rinse liquid dilution ofsucceeding sample liquids.

Sample liquid edge detector 54 is electrically disabled by systemcontroller 350 during sample liquid aspiration path rinse as describedto prevent the actuation of sampling valve 30 by that detector uponrinse liquid passage through the latter.

Following particularly thorough rinsing of the closed sample containersample liquid aspiration path as described, solenoid 290 is activated bysystem controller 350 on line 376 to close valve 280 as shown bywaveform 396 in FIG. 16, and solenoid 286 is activated by systemcontroller 350 on line 372 to open sample liquid drain valve 276 asshown by waveform 398 in FIG. 16, thereby draining the remaining sampleliquid 410 from the dispensing well 36 to vacuum and waste throughconduit 44, sampling valve 30, and drain conduit 50. Shortly thereafter,controller 350 activates solenoids 286 and 292 on lines 372 and 378 tore-close valve 276 and open dispensing well rinse liquid control valve282, as respectively shown by waveforms 398 and 400 in FIG. 16, therebycommencing the flow of rinse liquid from source 310 (FIG. 14) into thedispensing well 36 to fill the well bore 264 with rinse liquid to atleast the level therein just occupied by the sample liquid 410 fromclosed sample tube 128. Controller 350 then activates solenoid 286 online 372 to re-open drain valve 276 as shows by waveform 398 to flow theaccumulated rinse liquid, followed by ambient air for drying, from wellbore 264 through conduit 44, sample liquid particle trap 56, andsampling valve 30--thereby forcibly backflushing the same against theinitial direction of flow of the sample liquid 410 therethrough--anddrain conduit 50 to vacuum and waste. As a result, the hydrophobicisolation liquid-coated surfaces of dispensing well bore 264, conduit44, and the relevant internal passages of sampling valve 30, areforcibly backflushed and cleansed of virtually all residue of sampleliquid 410, to again virtually eliminate the contamination thereby ofthe sample liquid from a succeeding closed sample liquid container onuniversal carrier block 22.

Of course, the extremely small quantity of the isolation liquid fromsource 330 (FIG. 14) supplied as previously described in detail withreference to waveform 404 of FIG. 16 to the bore 264 of the dispensingwell 36, flows with this rinse liquid, although at a much lower flowrate, to replenish the extremely thin isolation liquid layer on thehydrophobic surfaces of dispensing well bore 264, conduit 44, and therelevant passages in sampling valve 30.

Operationn of the integrated sampler 20 of my invention continues asdescribed until sampling in turn from all sample liquid containers, bethe same open or closed, on the universal carrier block 22 has beenaccomplished as described; it being clear to those skilled in this artthat, in actual practice, a plurality, for example twenty, of theuniversal carrier blocks 22, each mounting six sample containers, wouldbe provided and indexed in sequence by drive motor 213 under the controlof system controller 350 vis-a-vis sample analysis system probe 37 asdescribed to accomplish a full sampling "run".

Under all of the above circumstances, it will be clear that, forrepresentative use as described with a hydrophobic sample analysis probeof the nature disclosed in U.S. Pat. No. 4,121,466 which also utilizesan isolation liquid for purposes of sample liquid carryoverminimization, the new and improved integrated sampler 20 of my inventioninsures sample liquid carryover minimization from the point of sampleliquid supply to the probe for aspiration, be it from a closed or opensample liquid container, virtually to the point of sample liquidanalysis by the analysis system 270; thereby contributing verysignificantly to the overall accuracy of the sample liquid analystsresults.

Various changes may of course be made in the apparatus and method of myinvention as representatively disclosed herein without departing fromthe spirit and scope of that invention as defined in the appendedclaims.

What is claimed is:
 1. In sample liquid container support apparatus foruse in a sampler, the improvements comprising, said support apparatuscomprising, a plurality of sample liquid container mounting means eachof which is operable to mount either a closed sample liquid container oran open sample liquid container, and means on said support apparatus foroperatively connecting said support apparatus to a sampler for use insaid sampler.
 2. In sample liquid container support apparatus as inclaim 1, the improvements further comprising, each of said sample liquidcontainer mounting means forming a sample liquid container mountingaperture for the mounting of a sample liquid container therein.
 3. Insample liquid container support apparatus as in claim 2, theimprovements further comprising, said sample liquid container mountingapertures being generally vertically oriented, with each of saidapertures being adapted to mount a closed sample liquid containertherein with the closed container end down, or an open sample liquidcontainer therein with the open container end up.
 4. In sample liquidcontainer support apparatus as in claim 2, the improvements furthercomprising, closed sample liquid container retaining means operativelyassociated with said sample liquid container mounting apertures andoperable to retain closed sample liquid containers therein.
 5. In sampleliquid container support apparatus as in claim 1, the improvementsfurther comprising, said sample liquid container mounting meanscomprising means for mounting said open sample liquid containers atessentially the same level relative to said support means.
 6. In amethod for integrated sample liquid containers for use in a sampler, theimprovements comprising, the steps of, providing a plurality of sampleliquid container mounting means on the same sample liquid containersupport means, and mounting both closed sample liquid containers andopen sample liquid containers on said same sample liquid containersupport means to said integrated sampler.
 7. In a method as in claim 6,the improvements further comprising, the steps of, mounting closedsample liquid containers and open sample liquid containers on a randombasis on said same sample liquid container support means.
 8. In a methodas in claim 6, the improvements further comprising, the steps ofmounting said closed sample liquid containers on said sample liquidcontainer support means comprising the generally vertical mounting ofthe same thereon with the closed sample liquid container end down.
 9. Ina method as in claim 6, the improvements further comprising, the stepsof, retaining said closed sample liquid containers mounted on saidsample liquid container support means.